TY - JOUR
T1 - Expression of hypoxia-inducible factors, regulators, and target genes in congenital diaphragmatic hernia patients
AU - Van Der Horst, Irene W.J.M.
AU - Rajatapiti, Prapapan
AU - Van Der Voorn, Paul
AU - Van Nederveen, Francien H.
AU - Tibboel, Dick
AU - Rottier, Robbert
AU - Reiss, Irwin
AU - De Krijger, Ronald R.
PY - 2011/12/1
Y1 - 2011/12/1
N2 - Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia and pulmonary hypertension and has high morbidity and mortality rates. The cause and pathophysiology of CDH are not fully understood. However, impaired angiogenesis appears to play an important role in the pathophysiology of CDH. Therefore, we examined different components of an important pathway in angiogenesis: hypoxia-inducible factors (HIFs); HIF regulators von Hippel - Lindau (VHL) and prolyl 3-hydroxylase (PHD3); and HIF target genes vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR-2). Quantitative polymerase chain reaction of lung tissue showed a significantly decreased expression of VEGF-A mRNA in the alveolar stage of lung development in CDH patients compared with matched control patients. In the canalicular stage, no differences for VEGF-A were seen between the lungs of CDH patients and those of control patients. Other components of angiogenesis (VHL, HIF-1α, HIF-2α, HIF-3α, VEGFR-2 mRNA, PHD3 protein) that were analyzed showed no differences in expression between CDH and control patients, independent of the developmental stage. A lower expression of VEGF mRNA in CDH patients in the alveolar stage, possibly as a result of downregulation of HIF-2α might indicate a role for these factors in the pathophysiology of CDH.
AB - Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia and pulmonary hypertension and has high morbidity and mortality rates. The cause and pathophysiology of CDH are not fully understood. However, impaired angiogenesis appears to play an important role in the pathophysiology of CDH. Therefore, we examined different components of an important pathway in angiogenesis: hypoxia-inducible factors (HIFs); HIF regulators von Hippel - Lindau (VHL) and prolyl 3-hydroxylase (PHD3); and HIF target genes vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR-2). Quantitative polymerase chain reaction of lung tissue showed a significantly decreased expression of VEGF-A mRNA in the alveolar stage of lung development in CDH patients compared with matched control patients. In the canalicular stage, no differences for VEGF-A were seen between the lungs of CDH patients and those of control patients. Other components of angiogenesis (VHL, HIF-1α, HIF-2α, HIF-3α, VEGFR-2 mRNA, PHD3 protein) that were analyzed showed no differences in expression between CDH and control patients, independent of the developmental stage. A lower expression of VEGF mRNA in CDH patients in the alveolar stage, possibly as a result of downregulation of HIF-2α might indicate a role for these factors in the pathophysiology of CDH.
KW - Congenital diaphragmatic hernia
KW - Hypoxia-inducible factors
KW - Lung development
KW - Prolyl 4-hydroxylase
KW - Vascular endothelial growth factor
KW - Von Hippel-Lindau protein
UR - http://www.scopus.com/inward/record.url?scp=84855387534&partnerID=8YFLogxK
U2 - 10.2350/09-09-0705-OA.1
DO - 10.2350/09-09-0705-OA.1
M3 - Article
C2 - 21671771
AN - SCOPUS:84855387534
SN - 1093-5266
VL - 14
SP - 384
EP - 390
JO - Pediatric and Developmental Pathology
JF - Pediatric and Developmental Pathology
IS - 5
ER -